Margaret Fahnestock, Ph.D.
McMaster University
Hamilton, Ontario, Canada

2007 Investigator-Initiated Research Grant

Brain-derived neurotrophic factor (BDNF) is a potent neuroprotective protein in the brain. In Alzheimer’s disease, however, BDNF levels are lower than normal. Although this loss occurs early in the disease process and correlates with the degree of cognitive impairment, it is not clear what causes BDNF loss or whether it is a cause or effect of Alzheimer’s.

Margaret Fahnestock, Ph.D., and colleagues plan to investigate the cause of BDNF loss in Alzheimer’s disease. They will investigate whether beta-amyloid protein fragments or abnormal tau proteins — both key features of the disease — influence BDNF production and function. The researchers will address this using several approaches: (1) use cultured neurons to measure how beta-amyloid affects BDNF production and levels, (2) determine levels of BDNF in tissue samples taken from people diagnosed with tau-related disease to investigate if tau can affect BDNF and (3) investigate how BDNF changes in mice engineered to overproduce either beta-amyloid or tau.

The researchers believe that this work will lead to a much better understanding of how BDNF relates to the pathology of Alzheimer’s disease and other neurodegenerative disorders. It may also reveal new diagnostic or therapeutic targets.